The infectious agents causing transmissible spongiform encephalopathies (TSE agents or prions) are notoriously difficult to inactivate completely. Previous studies indicated that drying infected tissues increased the resistance of the TSE agents to inactivation. We modified a test originally designed to evaluate effects of disinfectants on conventional viruses to detect residual infectivity remaining on glass surfaces after various treatments intended to inactivate or remove TSE agents (using the 263K strain of hamster-adapted scrapie agent as a model). The modified method employs only disposable equipment to reduce opportunities for cross contamination. Preliminary studies with suspensions of conventional viruses showed little within-test variability but significant between-test variability, so that a reference sham-treated preparation of scrapie-infected tissue suspension was included and titrated in each test. Control treatments with diluents containing no disinfectants removed only negligible amounts of scrapie infectivity from surfaces. As previously observed, residual scrapie infectivity was detected after autoclaving at 134o C for 1 hr. Early results suggest that treatments with NaOH and NaOCl were more effective. A variety of other decontamination regimens are under study, including detergents, phenolic disinfectants and combinations of agents with and without autoclaving. This project is to be continued in FY 00.